Posted by Sunnely on July 22, 2001, at 21:22:12
In reply to Re: Tricyclic Serum Levels, posted by stjames on July 22, 2001, at 16:24:13
Although not all psychotropic drugs require therapeutic drug monitoring (TDM), there are situations in which psychotropic TDM is useful:
1. When the possibility of genetic polymorphism exists in one of the cytochrome P450 enzyme families, rendering them extensive metabolizers (EMs) or poor metabolizers (PMs) of certain drugs. For example, about 8% of Caucasians are genetically deficient in CYP2D6 enzymes making them more prone to dangerous blood levels of a psychotropic drug that depends on this enzyme for metabolism such as desipramine (Norpramin). Genetic deficiency of CYP2D6 may also explain the lack of response to adequate dosage of analgesics such as codeine preparations and tramadol (Ultram) as these drugs require the presence of CYP2D6 to be converted to their active metabolites, morphine and M1, respectively.
2. Drug-drug interactions. Certain medications can affect the metabolism of some of the psychotropic drugs. For example, carbamazepine (Tegretol) can decrease the blood levels of haloperidol (Haldol) by as much as 50% via induction of hepatic metabolism leading to decreased blood level of haloperidol and subsequent psychotic relapse. On the other hand, cimetidine (Tagamet) increases the blood level of haloperidol leading to increased haloperidol side effects (e.g., tremor, rigidity, motor restlessness). Fluoxetine (Prozac) and paroxetine (Paxil) can increase the blood level of desipramine (Norpramin) leading to increased desipramine side effects and potentially dangerous electrocardiogram abnormality.
The antibiotic ciprofloxacin (Cipro) and the antidepressant fluvoxamine (Luvox) can significantly increase the blood level of clozapine (Clozaril), and also olanzapine (Zyprexa), which can cause increase side effects (even acute delirium and/or seizures with clozapine). On the other hand, cigarette smoking can decrease the blood levels of clozapine and olanzapine leading to loss of effectiveness and psychotic relapse. Conversely, abrupt discontinuation of cigarette smoking may lead to an increase in clozapine (and olanzapine) blood level leading to toxicity.
3. For certain drugs which induce their own metabolism resulting in declining blood levels (e.g., carbamazepine or Tegretol). Tegretol is an "autoinducer," it induces its own metabolism.
4. When drug toxicity may be confused with the disease being treated. Akathisia (motor restlessness) and anxiety/agitation are difficult to differentiate. Increasing the dose of the antipsychotic drug may worsen the akathisia. Checking the antipsychotic blood level (e.g., haloperidol) may help resolve this problem.
Dry mouth, constipation, and lethargy can be symptoms of depression as well as adverse effects of TCAs. Without TDM, the doctor may increase the dose of TCA due to presumed worsening of the mood disorder, leading to further increase in TCA toxicity.
5. Suspected noncompliance. Forty percent of patients are noncompliant with psychotropic drugs. Erratic compliance can lead to subtherapeutic blood concentrations, leading to prolonged duration of illness.
6. For drugs with narrow therapeutic index (margin of safety between therapeutic blood level and toxic blood level) such as lithium. This is of particular importance especially in the elderly patients, those with concomitant medical illness, taking other drugs, and children.
7. For drugs whose activity is dependent upon the parent and active metabolites (e.g., several TCAs, antipsychotics, and anti-anxiety drugs).
8. For maintenance treatment when minimum effective blood level is required for prophylaxis (e.g., lithium). Although lithium levels between 0.8 - 1.2 is the general guideline to the treatment of acute mania of bipolar disorder, lower blood levels may suffice once mania has been stabilized.
9. For emergency management of psychotropic drug overdose. For example, serial blood levels (among other measures) of lithium or TCA in the medical management in cases of acute overdoses are of utmost importance.
10. Prediction of dose needed to achieve a therapeutic blood level at steady state. For example, following a single 600-mg dose of lithium, a 24-hour blood lithium level can be used to determine the dosage that will be required to achieve a steady-state blood level between 0.6 to 1.2. Similar nanograms are available for some TCAs, although therapeutic blood levels for these drugs are less well established. Also, checking for valproate blood level a few days after insitituting a loading dose of Depakote.
11. To document the level of a therapeutic dose for an individual patient, especially those patients requiring unusually high or low doses (may be helpful for legal purpose). For example, some extremely rapid metabolizers require unusually high doses that exceed usual guide; slow metabolizers should be treated with extremely low doses that would usually be considered subtherapeutic. Lack of TDM in the case of a sudden death with substantially elevated postmortem blood drug concentrations may be seen as negligence.
12. Minimize cost. For example, noncompliance and subtherapeutic blood levels usually delay the improvement of the illness, leading to prolonged hospital stay or additional outpatient visits. Identifying excessive psychotropic blood levels avoids toxicity, further avoiding unnecessary or prolonged hospitalization (and additional and costly laboratory tests).
SOME TIPS for TDM:
1. Drug levels are most reliably measured as "trough" levels; sample is drawn sometime after the elimination commences, usually 10 to 12 hours after the last dose. It is usually drawn in the morning, before the morning dose is taken, if one is scheduled.
2. The patient should be at pharmacokinetically stable blood level; after at least 4 to 5 half lives before checking for TDM. However, a doctor can order a psychotropic blood level anytime if he/she suspects toxicity, noncompliance, or drug-drug interactions.
3. As with any laboratory test, results should be interpreted with the patient's clinical condition in mind. For example, even if a patient's lithium blood level says 0.8-1.2 (within therapeutic range) but the patient is experiencing symptoms such as lethargy, confusion, increased tremor, unsteadiness, diarrhea, primary consideration should be lithium toxicity despite the "normal" lithium level. Lithium must be stopped immediately.
4. If you adjust for an interactive drug and take the interactive drug away, you've got to readjust. (For example, effect of cigarette smoking and abrupt discontinuation of smoking on certain drugs such as clozapine or olanzapine.)
> > Where is your proof of what you say?
> >
>
> Look to the internet or "Listening to Prozac"
> Blood levels of TCA's are not very predictive
> of outcome. After all it is not blood that has the synapse.
> They are done just to get an idea if
> a patient is a rapid metabolizer.
>
> James
poster:Sunnely
thread:70659
URL: http://www.dr-bob.org/babble/20010720/msgs/71449.html